title: TGFβ1 suppresses vascular smooth muscle cell motility by expression of N-cadherin.
abstract: Neointimal formation in atheromatous blood vessels is associated with both growth factor-induced differentiation of smooth muscle cells and endothelial-to-mesenchymal transition. Transforming growth factor beta (TGFβ)-signaling is well known to play a critical role in the regulation of vessel remodeling as well as in atherosclerosis and restenosis. Here, we investigated the role of TGFβ1 and N-cadherin on the differentiation and migration of human vascular smooth muscle cells (VSMC). TGFβ1-treatment of cultured VSMC reduced their migratory activity as determined in cell migration assays. This reduced migration correlated with increased concentration of N-cadherin on mRNA and protein level. The TGFβ1-induced increase of N-cadherin was sensitive against pharmacological inhibition of the ALK5 TGFβ receptor and was accompanied by TGFβ1-induced expression of the transcription factor snail1. Activation of N-cadherin by using a HAV-containing peptide of N-cadherin also decreased the migration of VSMC. N-cadherin-mediated suppression of VSMC migration was associated with an increased activity of RhoA, which is activated by binding of the HAV peptide to N-cadherin. Our results demonstrate that TGFβ1 induces the differentiation of primary VSMC cells by Smad2/3-dependent up-regulation of the transcription factor snail1 and subsequently of N-cadherin, leading to inhibition of VSMC migration by RhoA-dependent modulation of the actin cytoskeleton.
authors.affiliation: Internal Medicine I, Nephrology, University of Ulm, Albert-Einstein-Allee, Germany.
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Nuessle
authors.forename: Klaudia
authors.initials: K
authors.lastname: Giehl
authors.forename: Rosa
authors.initials: R
authors.lastname: Herzog
authors.forename: Sylvia
authors.initials: S
authors.lastname: Stracke
authors.forename: Andre
authors.initials: A
authors.lastname: Menke
mesh_terms: D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007150:Immunohistochemistry; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D016212:Transforming Growth Factor beta; D020741:rho GTP-Binding Proteins